Waldenstrom's macroglobulinemia (W.M.) is a rare and complex lymphoproliferative malignancy often associated with an apparent excess of lymphoproliferative neoplasms, autoimmune disorders, and immunologic abnormalities in first-degree relatives. The primary objective of the proposed case-control and family study is to examine by medical chart review and interview the postulated association between W.M. and chronic antigenic stimulation secondary to infections, inflammatory processes, autoimmune diseases and chronic drug use and to determine whether there is an increased proportion of lymphoproliferative malignancies and auto-immune diseases in first-degree relatives of W.M. cases compared with first-degree relatives of controls. A second objective is to determine whether certain HLA antigen types differ in frequency between cases and controls and whether certain HLA antigen types occur in excess among persons with W.M. and their first-degree relatives with W.M., other lymphoproliferative malignancies or autoimmune diseases in families with two or more cases of these diseases compared with controls. A third objective is to examine immunoglobulin profiles and immunoelectrophoresis patterns among cases and first-degree relatives and to correlate findings with epidemiologic and HLA characteristics. Finally we will compare risk factors for W.M. with those for chronic lymphocytic leukemia to determine if epidemiologic similarities parallel histopathologic similarities. We will identify all W.M. cases diagnosed at ten Baltimore hospitals from July 1, 1975 through December 31, 1982. For the case-control study each case will be individually matched (by age, sex, race, hospital and date of admission) with three controls: one with any malignancy other than a lymphoproliferative malignancy, one with any non-malignant disease, and a third with CLL. For the family studies we will interview each living first-degree relative or, if dead, their next-of-kin, and draw blood for HLA and immunoglobulin studies for each living first-degree relative. The proposed integrated, in-depth epidemiologic and immunogenetic study of W.M. is a unique approach to increase knowledge of the relationship between etiologic and pathophysiologic characteristics of Waldenstrom's macroglobulinemia.